The ERA5 global reanalysis Hersbach, Hans; Bell, Bill; Berrisford, Paul ...
Quarterly journal of the Royal Meteorological Society,
July 2020 Part A, Letnik:
146, Številka:
730
Journal Article
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Within the Copernicus Climate Change Service (C3S), ECMWF is producing the ERA5 reanalysis which, once completed, will embody a detailed record of the global atmosphere, land surface and ocean waves ...from 1950 onwards. This new reanalysis replaces the ERA‐Interim reanalysis (spanning 1979 onwards) which was started in 2006. ERA5 is based on the Integrated Forecasting System (IFS) Cy41r2 which was operational in 2016. ERA5 thus benefits from a decade of developments in model physics, core dynamics and data assimilation. In addition to a significantly enhanced horizontal resolution of 31 km, compared to 80 km for ERA‐Interim, ERA5 has hourly output throughout, and an uncertainty estimate from an ensemble (3‐hourly at half the horizontal resolution). This paper describes the general set‐up of ERA5, as well as a basic evaluation of characteristics and performance, with a focus on the dataset from 1979 onwards which is currently publicly available. Re‐forecasts from ERA5 analyses show a gain of up to one day in skill with respect to ERA‐Interim. Comparison with radiosonde and PILOT data prior to assimilation shows an improved fit for temperature, wind and humidity in the troposphere, but not the stratosphere. A comparison with independent buoy data shows a much improved fit for ocean wave height. The uncertainty estimate reflects the evolution of the observing systems used in ERA5. The enhanced temporal and spatial resolution allows for a detailed evolution of weather systems. For precipitation, global‐mean correlation with monthly‐mean GPCP data is increased from 67% to 77%. In general, low‐frequency variability is found to be well represented and from 10 hPa downwards general patterns of anomalies in temperature match those from the ERA‐Interim, MERRA‐2 and JRA‐55 reanalyses.
This paper presents a comprehensive overview of the ERA5 global reanalysis from 1979 onwards, which is produced at ECMWF as part of the Copernicus Climate Change Service. It provides a detailed record of the three‐dimensional atmosphere, land surface and ocean waves at an hourly temporal resolution. Compared to its predecessor ERA‐Interim, ERA5 has a much‐increased horizontal resolution and benefits from 10 more years of R&D, which includes an uncertainty estimate from an underlying ensemble of 4D‐Var data assimilation systems.
Infectious Agents and Neurodegeneration De Chiara, Giovanna; Marcocci, Maria Elena; Sgarbanti, Rossella ...
Molecular neurobiology,
12/2012, Letnik:
46, Številka:
3
Journal Article
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A growing body of epidemiologic and experimental data point to chronic bacterial and viral infections as possible risk factors for neurodegenerative diseases, including Alzheimer’s disease, ...Parkinson’s disease and amyotrophic lateral sclerosis. Infections of the central nervous system, especially those characterized by a chronic progressive course, may produce multiple damage in infected and neighbouring cells. The activation of inflammatory processes and host immune responses cause chronic damage resulting in alterations of neuronal function and viability, but different pathogens can also directly trigger neurotoxic pathways. Indeed, viral and microbial agents have been reported to produce molecular hallmarks of neurodegeneration, such as the production and deposit of misfolded protein aggregates, oxidative stress, deficient autophagic processes, synaptopathies and neuronal death. These effects may act in synergy with other recognized risk factors, such as aging, concomitant metabolic diseases and the host’s specific genetic signature. This review will focus on the contribution given to neurodegeneration by herpes simplex type-1, human immunodeficiency and influenza viruses, and by
Chlamydia pneumoniae
.
This paper reports on a quantitative estimation of the risk to residents at the toe of Mount Albino, a carbonatic relief covered by shallow deposits of pyroclastic soils, which threatens the ...municipality of Nocera Inferiore (southern Italy). The quantitative risk analysis (QRA) focuses on one type of mass transport phenomena typical for the context at hand, namely the hyperconcentrated flows. The methodological approach includes three main steps: hazard analysis, consequence analysis and risk estimation. Based on historical incident data, the hazard analysis makes use of a high-resolution digital terrain model and advanced models that incorporate relevant geological and geotechnical input data collected via in situ investigations and laboratory tests. The consequence analysis takes into account information on the exposed persons (age, gender) and their vulnerability. The estimated risk to life is calculated at the individual level (risk to the average and most exposed person). The reported procedure is one of the first QRA’s applications to instabilities which potentially affect natural slopes in Italy, and it was successfully used as technical basis for a public participatory process in Nocera Inferiore, designed and developed to support decisions about risk mitigation measures.
Herpes simplex virus type 1 (HSV-1) is a DNA neurotropic virus, usually establishing latent infections in the trigeminal ganglia followed by periodic reactivations. Although numerous findings ...suggested potential links between HSV-1 and Alzheimer's disease (AD), a causal relation has not been demonstrated yet. Hence, we set up a model of recurrent HSV-1 infection in mice undergoing repeated cycles of viral reactivation. By virological and molecular analyses we found: i) HSV-1 spreading and replication in different brain regions after thermal stress-induced virus reactivations; ii) accumulation of AD hallmarks including amyloid-β protein, tau hyperphosphorylation, and neuroinflammation markers (astrogliosis, IL-1β and IL-6). Remarkably, the progressive accumulation of AD molecular biomarkers in neocortex and hippocampus of HSV-1 infected mice, triggered by repeated virus reactivations, correlated with increasing cognitive deficits becoming irreversible after seven cycles of reactivation. Collectively, our findings provide evidence that mild and recurrent HSV-1 infections in the central nervous system produce an AD-like phenotype and suggest that they are a risk factor for AD.
Among the multiple factors concurring to Alzheimer's disease (AD) pathogenesis, greater attention should be devoted to the role played by infectious agents. Growing epidemiological and experimental ...evidence suggests that recurrent herpes simplex virus type-1 (HSV-1) infection is a risk factor for AD although the underlying molecular and functional mechanisms have not been fully elucidated yet. Here, we review literature suggesting the involvement of HSV-1 infection in AD also briefly mentioning possible pharmacological implications of these findings.
Decisions associated with life safety risk management of natural hazards can involve significant potential consequences for public safety. Given possible limitations to available societal resources, ...it is therefore necessary to establish a clear and rational basis for the allocation of resources towards risk management. A viable approach for utilising life safety risk assessment in public safety decisions that are aimed at improving the welfare of the public and other stakeholders is described in this paper. This approach is conceptually based on the principles of the Life Quality Index (LQI) (Nathwani et al. in Affordable safety by choice: the life quality method. University of Waterloo, Waterloo,
1997
; Nathwani et al. in Engineering decisions for life quality: how safe is safe enough? Springer, London,
2009
). A case study involving the cost–benefit analysis of selected packages of measures for reducing the risks posed by different rainfall-induced flow-like phenomena—which include hyperconcentrated flows, debris flows and landslides on open slopes—in the municipality of Nocera Inferiore (located in the Campania region in southern Italy) is then described. As demonstrated through the case study, the approach enables a clear evaluation of the efficiency and acceptability of the risk mitigation packages and provides vital decision support in their prioritisation and optimisation.
Herpes simplex virus 1 (HSV-1) is a widespread neurotropic virus establishing a life-long latent infection in neurons with periodic reactivations. Recent studies linked HSV-1 to neurodegenerative ...processes related to age-related disorders such as Alzheimer's disease. Here, we explored whether recurrent HSV-1 infection might accelerate aging in neurons, focusing on peculiar marks of aged cells, such as the increase in histone H4 lysine (K) 16 acetylation (ac) (H4K16ac); the decrease of H3K56ac, and the modified expression of Sin3/HDAC1 and HIRA proteins. By exploiting both in vitro and in vivo models of recurrent HSV-1 infection, we found a significant increase in H4K16ac, Sin3, and HDAC1 levels, suggesting that the neuronal response to virus latency and reactivation includes the upregulation of these aging markers. On the contrary, we found a significant decrease in H3K56ac that was specifically linked to viral reactivation and apparently not related to aging-related markers. A complex modulation of HIRA expression and localization was found in the brain from HSV-1 infected mice suggesting a specific role of this protein in viral latency and reactivation. Overall, our results pointed out novel molecular mechanisms through which recurrent HSV-1 infection may affect neuronal aging, likely contributing to neurodegeneration.
Influenza virus infection induces oxidative stress in host cells by decreasing the intracellular content of glutathione (GSH) and increasing reactive oxygen species (ROS) level. Glucose-6-phosphate ...dehydrogenase (G6PD) is responsible for the production of reducing equivalents of nicotinamide adenine dinucleotide phosphate (NADPH) that is used to regenerate the reduced form of GSH, thus restoring redox homeostasis. Cells deficient in G6PD display elevated levels of ROS and an increased susceptibility to viral infection, although the consequences of G6PD modulation during viral infection remain to be elucidated. In this study, we demonstrated that influenza virus infection decreases G6PD expression and activity, resulting in an increase in oxidative stress and virus replication. Moreover, the down regulation of G6PD correlated with a decrease in the expression of nuclear factor erythroid 2-related factor 2 (NRF2), a key transcription factor that regulates the expression of the antioxidant response gene network. Also down-regulated in influenza virus infected cells was sirtuin 2 (SIRT2), a NADPH-dependent deacetylase involved in the regulation of G6PD activity. Acetylation of G6PD increased during influenza virus infection in a manner that was strictly dependent on SIRT2 expression. Furthermore, the use of a pharmacological activator of SIRT2 rescued GSH production and NRF2 expression, leading to decreased influenza virus replication. Overall, these data identify a novel strategy used by influenza virus to induce oxidative stress and to favor its replication in host cells. These observations furthermore suggest that manipulation of metabolic and oxidative stress pathways could define new therapeutic strategies to interfere with influenza virus infection.
Protein phosphorylation is the main signaling system known to trigger synaptic changes underlying long-term potentiation (LTP). The timing of these phosphorylations plays an essential role to ...maintain the potentiated state of synapses. However, in mice a simultaneous analysis of phosphorylated proteins during early-LTP (E-LTP) has not been thoroughly carried out. Here we described phosphorylation changes of αCaMKII, ERK1/2, PKB/Akt and CREB at different times after E-LTP induced at Schaffer collateral/commissural fiber-CA1 synapses by 1 s 100 Hz tetanic stimulation in mouse hippocampal slices. We found that phosphorylation levels of all the molecules examined rapidly increased after tetanisation and remained above the basal level up to 30 min. Notably, we observed a sustained increment in the phosphorylation level of Akt at Ser473, whereas the phosphorylation level of Akt at Thr308 was unchanged. Unexpectedly, we also detected a marked increase of CREB target genes expression levels, c-fos, Egr-1 and exon-III containing BDNF transcripts. Our findings, besides providing a detailed timing of phosphorylation of the major kinases involved in E-LTP in mice, revealed that a modest LTP induction paradigm specifically triggers CREB-mediated gene expression.
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